Toxicometabolomics: Identification of markers of chronic exposure to low doses of aliphatic hydrocarbons

Abstract

The metabolic profile of plasma of white non-linear rats was investigated under normal conditions and after chronic inhalation exposure to low doses of aliphatic hydrocarbons (HC) with the number of carbon atoms from 6 to 10. The metabolic profile was determined by a combination of gas chromatography/mass spectrometry and high-performance liquid chromatography/high-resolution mass spectrometry with the subsequent use of chemometrical methods for data treatment and presentation. It was shown that continuous 90-day exposure to a mixture of C₆–C₁₀ saturated hydrocarbons at a concentration of 160 ± 20.5 mg/m³ leads to various metabolic impairments in the liver and kidneys. Exposure to hydrocarbon mixtures at doses of 31.4 ± 5.6 and 5.2 ± 1.8 mg/m³ evoked significantly smaller changes. Novel metabolic markers of the toxic effect of low concentrations of C6–C10 aliphatic hydrocarbons were revealed. The concentration ratio of pyrophosphoric and oxalic acids in rat blood plasma was found to be the most sensitive marker called a pyrophosphate index. A hypothesis was proposed about the disturbance of the redox balance as a leading pathogenetic mechanism of neuropathies and concomitant pathologies associated with chronic HC intoxication.